Transgenic mouse technology can be utilized to produce animals expressing a foreign gene to high levels of its RNA and protein. The objective of this project is to generate mice that contain an abnormal beta-globin gene (beta-sickle Antilles). This gene has two mutations and generates sickle cell anemia in a heterozygous individual. High level expression of the gene is obtained by inserting the dominant control region from the human beta globin locus in cis to the Antilles gene. This dominant control region allows high level globin expression to occur. The human alpha-globin gene is also inserted in cis in order to generate mice that can produce high levels of beta sickle Antilles and human alpha globins. Three independent transgenic mouse lines that express both human globin genes have been generated. Expression levels of human alpha globin RNA are high but levels of the human beta sickle Antilles RNA have been consistently low. Homozygous mice with these constructs cannot be generated easily and there is a genetic evidence that the beta sickle Antilles gene may generate harmful effects during development of the mouse. Due to imbalance of alpha and beta globin chains there is increased fetal demise even in heterozygous animals. This effect is more pronounced when the transgenics are bred on a background of beta thalassemic mice.